Structural highlights
Function
[CDC13_YEAST] Single-stranded telomeric DNA-binding protein that regulates telomere replication. Has a role in both positive and negative regulation. Promotes [TG(1-3)] strand lengthening via interaction with EST1. Promotes [C(1-3)A] strand re-synthesis by DNA polymerase alpha via interaction with POL1. Negatively regulates telomere elongation of the G strand via binding with STN1 thereby inhibiting telomerase activity.[1] [2] [3] [DPOA_YEAST] Catalytic component of DNA polymerase alpha, which in complex with DNA primase (DNA polymerase alpha:primase) consitutes a replicative polymerase. POL1 has a role in promoting telomere replication during interaction with CDC13.[4]
Publication Abstract from PubMed
Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, our structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase alpha (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.
Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase alpha,Sun J, Yang Y, Wan K, Mao N, Yu TY, Lin YC, Dezwaan DC, Freeman BC, Lin JJ, Lue NF, Lei M Cell Res. 2010 Sep 28. PMID:20877309[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chandra A, Hughes TR, Nugent CI, Lundblad V. Cdc13 both positively and negatively regulates telomere replication. Genes Dev. 2001 Feb 15;15(4):404-14. PMID:11230149 doi:10.1101/gad.861001
- ↑ Meier B, Driller L, Jaklin S, Feldmann HM. New function of CDC13 in positive telomere length regulation. Mol Cell Biol. 2001 Jul;21(13):4233-45. PMID:11390652 doi:10.1128/MCB.21.13.4233-4245.2001
- ↑ Qi H, Zakian VA. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000 Jul 15;14(14):1777-88. PMID:10898792
- ↑ Qi H, Zakian VA. The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev. 2000 Jul 15;14(14):1777-88. PMID:10898792
- ↑ Sun J, Yang Y, Wan K, Mao N, Yu TY, Lin YC, Dezwaan DC, Freeman BC, Lin JJ, Lue NF, Lei M. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase alpha Cell Res. 2010 Sep 28. PMID:20877309 doi:10.1038/cr.2010.138
